Purine compounds and method for the treatment of cancer

Abstract

The present disclosure relates to novel compound of Formula I, (I) or a pharmaceutically acceptable salt or solvate thereof; wherein Ra, Rb, Rc, Rd, ring A and ring B are as defined herein, pharmaceutical compositions containing same and methods for the treatment of cancer using same.

The invention claimed is: 
     
       1. A compound of formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof;
 wherein 
 Ra is independently H, a straight or branched alkyl substituted or not with a halogen, cycloalkyl of 3 to 6 carbon atoms, straight or branched alkoxy substituted or not with a halogen, heteroaryl or halogen, 
 Rb is H or a straight or branched alkyl of 1 to 6 carbon atoms, 
 Rc is H or a straight or branched alkyl of 1 to 6 carbon atoms substituted or not with a halogen, 
 Rd is H, halogen or an alkyl of 1 to 6 carbon atoms, 
 ring A is an optionally substituted saturated 5 to 7 membered cycloalkyl ring attached by a carbon atom of said ring to the nitrogen atom at the C-6 position of the purine core, and said ring A is optionally comprising one or two selenium atoms as ring constituting atoms, and wherein two selenium atoms are adjacent or non-adjacent, or ring A is an optionally substituted 5 to 7 members bridged bicycloalkyl, and 
 ring B is an optionally substituted saturated 5 to 7 membered heterocycloalkyl ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring optionally comprising one oxygen atom or one or two selenium atoms as ring constituting atoms, and wherein two selenium atoms are adjacent or non-adjacent, 
 provided at least one of ring A and ring B is comprising one or two ring constituting selenium atom. 
 
     
     
       2. The compound of  claim 1 , having the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       3. The compound of  claim 2 , wherein Ra is independently H, a straight alkyl or fluoroalkyl of 1-3 carbon atoms; branched alkyl or fluoroalkyl of 3 carbon atoms; straight alkoxy or fluoroalkoxy of 1-3 carbon atoms; branched alkoxy or fluoroalkoxy of 3 carbon atoms, cycloalkyl of 3 carbon atoms, heteroaryl of 5-6 members or fluoride atom. 
     
     
       4. The compound of  claim 2 , wherein Ra is independently H, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, ter-butyl, trifluoromethyl, trifluoromethoxy, methoxy, cyclopropyl, cyclobutyl, cyclopentyl cyclohexyl, heteroaryl of 5-6 members comprising at least one heteroatom selected from oxygen (O), and nitrogen (N); or fluoride atom. 
     
     
       5. The compound of  claim 2 , wherein ring A is an optionally substituted, saturated 5 to 7 members cycloalkyl or an optionally substituted bicyclo[2,2, 1] heptyl or bicyclo[3,1,1] heptyl. 
     
     
       6. The compound of  claim 2 , wherein ring A is a tetrahydroselenophene, a selenane, a diselenolane or a diselenane. 
     
     
       7. The compound of  claim 2 , wherein ring A is: 
       
         
           
           
               
               
           
         
       
     
     
       8. The compound of  claim 2 , wherein ring B is:
 an optionally substituted morpholinyl group; an optionally substituted saturated ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring is comprising 6 members, and is comprising one selenium atom as ring constituting atoms; or 
 an optionally substituted saturated ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring is comprising 7 members, and is comprising two selenium atoms as ring constituting atoms, and wherein said selenium atoms are adjacent. 
 
     
     
       9. The compound of  claim 2 , wherein ring B is a morpholinyl, a selenomorpholin-4yl of formula 
       
         
           
           
               
               
           
         
       
       or a 1,2-diselenazepan-5-yl of formula 
       
         
           
           
               
               
           
         
       
     
     
       10. The compound of  claim 1 , wherein each Ra is independently H, a straight alkyl of 1-3 carbon atoms, or branched alkyl of 3 carbon atoms, straight alkoxy of 1-3 carbon atoms or branched alkoxy of 3 carbon atoms, cycloalkyl of 3 carbon atoms, heteroaryl of 5-6 members or fluoride atom; Rb is H or methyl, ethyl, n-propyl, isopropyl; Rc is H or methyl, ethyl, n-propyl, isopropyl or trifluoromethyl; Rd is H, halogen, alkyl of 1 to 6 carbon atoms, and wherein:
 ring A is an optionally substituted, saturated 5 to 7 members cycloalkyl or an optionally substituted 5 to 7 members bridged bicycloalkyl and ring B is an optionally substituted saturated ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring is comprising 5 to 7 members, and is comprising one or two selenium atoms as ring constituting atoms, and wherein two selenium atoms are adjacent or non-adjacent; 
 ring A is an optionally substituted, saturated ring of 5 to 7 members, comprising one or two ring constituting selenium atom and ring B is an optionally substituted saturated ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring is comprising 5 to 7 members; or 
 ring A is an optionally substituted, saturated ring of 5 to 7 members, comprising one or two ring constituting selenium atom and ring B is an optionally substituted saturated ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring is comprising 5 to 7 members, and is comprising one or two selenium atoms as ring constituting atoms, and wherein two selenium atoms are adjacent or non-adjacent. 
 
     
     
       11. The compound of  claim 1 , wherein each Ra is H; Rb is H; Rc is H; Rd is H, ring A is an optionally substituted, saturated 5 to 7 members cycloalkyl or an optionally substituted 5 to 7 members bridged bicycloalkyl and ring B is an optionally substituted saturated ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring is comprising 5 to 7 members, and is comprising one or two selenium atoms as ring constituting atoms, and wherein two selenium atoms are adjacent or non-adjacent. 
     
     
       12. The compound of  claim 1 , wherein each Ra is H; Rb is H; Rc is H; Rd is H, ring A is an optionally substituted, saturated ring of 5 to 7 members, comprising one or two ring constituting selenium atom and ring B is an optionally substituted saturated ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring is comprising 5 to 7 members. 
     
     
       13. The compound of  claim 1 , wherein each Ra is H; Rb is H; Rc is H; Rd is H, ring A is an optionally substituted, saturated ring of 5 to 7 members, comprising one or two ring constituting selenium atom and ring B is an optionally substituted saturated ring attached by a nitrogen atom of said ring to a carbon atom of the phenylene residue, and wherein said ring is comprising 5 to 7 members, and is comprising one or two selenium atoms as ring constituting atoms, and wherein two selenium atoms are adjacent or non-adjacent. 
     
     
       14. The compound of  claim 1 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
       15. A pharmaceutical composition comprising a compound as defined in  claim 2 , or a pharmaceutically acceptable salt or solvate thereof, and one or more pharmaceutically acceptable carrier and/or excipient. 
     
     
       16. The pharmaceutical composition of  claim 15 , further comprising a therapeutically effective amount of at least one or more therapeutic agents selected from the group consisting of alkylating agents, anti-metabolites, plant alkaloids, terpenoids, vinca alkaloids, podophyllotoxin, taxanes, topoisomerase inhibitors, and cytotoxic antibiotics. 
     
     
       17. A method for treating cancer comprising administering to a patient in need thereof a therapeutically effective amount of the compound of  claim 2 . 
     
     
       18. The method of  claim 17 , comprising administering to a patient in need thereof a therapeutically effective amount of at least one or more therapeutic agents selected from the group consisting of alkylating agents, anti-metabolites, plant alkaloids, terpenoids, vinca alkaloids, podophyllotoxin, taxanes, topoisomerase inhibitors, and cytotoxic antibiotics. 
     
     
       19. The method of  claim 17  comprising co-modulating and/or co-inhibiting the function of Aurora A and Jak2 kinases. 
     
     
       20. The method of  claim 17  comprising reducing metastasis of metastatic cells of said cancer in said patient in need thereof.